1. Field of the Invention
The present invention relates to radioactive coating solutions, radioactive sols and sol-gels, methods used to form radioactive coatings on a variety of substrates, and to radioactive coated substrates. In particular, the present invention relates to a medical device, or a component thereof, having at least one radioactive coating layer thereon.
2. Description of Related Art
Metal coatings are used in a variety of industrial and engineering applications to provide, for example, resistance to corrosion and wear, enhanced lubricity and decorative appearance. Several methods are used to form metal coatings, including electrodeposition and electroless deposition. Electrodeposition depends on the use of applied voltage to produce metal deposition, while electroless deposition depends on chemical reactions (including the chemical reduction of a metal) independent of applied voltage. See, e.g., Dini, J. W., Developments and Trends in Electrodeposition, SAMPE Quarterly (1989) 28-32; and Ohno, I. Electrochemistry of Electroless Plating, Materials Science and Engineering, vol. A146 (1991) 33-49.
A wide variety of solutions for electrodeposition and electroless deposition are known, as theoretically any element or combination of elements, including metals and non-metals, can be added to a carrier metal to provide a suitable coating solution, wherein the carrier metal is present as an ion. In particular, metalloids including phosphorus and boron can be added to a carrier metal to provide a coating solution. Commonly used carrier metals include nickel, copper, cobalt, platinum, palladium, chromium, gold and silver. Particularly common are nickel and nickel alloy coating solutions, including nickel-phosphorus, nickel-boron, palladium-nickel, nickel-chromium, nickel-cobalt, nickel-phosphorus-boron, and copper-nickel chromium. Solutions are typically aqueous.
Electroless coatings are significantly more uniformly deposited than electrodeposited coatings, and are particularly desirable for coating complex shapes, including tubes and large components. Electroless deposition of nickel-phosphorus coatings, in particular, is well known. In general, electroless nickel phosphorus (ENP) coatings are dense, non-porous metal glass structures resembling polished stainless steel. ENP coatings typically contain between 3 and 13% by weight phosphorus, with the percentage significantly influencing both the chemical and physical properties of the coating. High phosphorus ENP coatings provide superior corrosion protection and are generally more continuous that lower phosphorus ENP coatings. R. P. Tracey, Practical Guide to Using N-P Electroless Nickel Coatings, Materials Selection and Design, 1990. ENP coatings are generally highly adhesive, providing resistance to chipping and peeling under extreme conditions. Electroless coatings may be amorphous or crystalline in structure
Materials to be coated by electroless deposition are commonly metal. Electroless coatings can be applied to most metals and alloys, including steel and stainless steel, iron, aluminum, titanium, magnesium, copper, brass, bronze and nickel. In some cases, in addition to cleaning and removing surface oxides, the metal or alloy must be pre-treated to provide a catalytic surface for the electroless coating. For example, for coating Elgiloy(trademark) with ENP, the surface must be coated (i.e., by electrodeposition or electroless deposition) with Ni prior to being coated with ENP. Electroless deposition may also be used to coat a variety of materials that are generally non-conductive, including plastics, glasses and ceramics, and composite materials. Coating of polymers genereally requires additional steps to activate the polymer surfaces. A variety of processes are known for making polymer surfaces catalytic to the coating process. A tin-palladium catalyst, for example, can be absorbed onto the surface of the substrate, or applied as a catalytic coating.
Electroless deposition is carried out by immersing the substrate to be coated in an coating solution or bath comprising a carrier metal ion and a reducing agent. In ENP coating solutions, the most common reducing agent is hypophosphite ion (H2PO2xe2x88x92). (Tracey, 1990). The metal ions are chemically reduced in the presence of the reducing agent and deposited onto the substrate surface. Deposition rates are typically 10-20 microns per hour. Typical commercial ENP coating are from about 2.5 to about 125 microns thick. (Tracey, 1990). Thicker coatings are typically required for rough surfaces.
Metal coatings may also be formed by electrodeposition. For example, nickel-phosphorous coatings may be produced by electrodeposition, and have comparable properties to those prepared via electroless deposition. Weil et al., Comparison of Some Mechanical and Corrosion Properties of Electroless and Electroplated Nickel-Phosphorous Alloys, Plating and Surface Finishing (Feb. 1989) 62-66.
Materials to be coated by electrodeposition include most metals and alloys, which in some cases must be clean and oxide free to provide a catalytic surface for electrodeposition. In certain circumstances, polymers may also be coated by electrodeposition. For example, plastics incorporating conductive particles can be coated by electrodeposition. Intrinsically conductive polymers may also be coated by electrodeposition. Generally, electrodeposition rates of Nixe2x80x94P are higher than normally obtained via electroless methods. Also, electroplating solutions are more stable and have fewer replenishment problems. However, electrodeposited Nixe2x80x94P does not coat complicated shapes with as uniform a thickness as ENP.
Electrodeposition is carried out by immersing the substrate to be coated in a coating solution or bath comprising a carrier metal ion and a radioisotope. Unlike electroless deposition, electrodeposition requires an applied current. In general, a reducing agent such as is necessary for electroless deposition is not required for electrodeposition, although reducing agents are not uncommonly present for electrodeposited Nixe2x80x94P coatings, for example.
Methods for producing radioactive metal articles are also known. For example, it is known to manufacture a metal article comprising a radioisotope, e.g., by alloying the radioisotope with a metal or alloy or by ion implantation with a radioactive element It is also known to manufacture non-radioactive metal articles which are subsequently made radioactive, e.g., by neutron bombardment. Each method of preparing radioactive metal articles, however, is associated with particular disadvantages. Manufacture of alloys using radioactive elements, for example, is problematic because many of the most desirable radioisotopes (e.g., P) show limited solubility as equilibrium alloying ingredients. Moreover, health physics safety issues associated with the manufacture of various articles effectively prohibit certain methods of manufacture.
The use of neutron bombardment to produce radioactive metal articles is similarly problematic, given limited access to nuclear reactors and tremendous costs. Neutron bombardment also constrains the size of components which can be irradiated. Moreover, neutron bombardment activates all components of the metal article that are susceptible to neutron activation, so that undesirable and potentially dangerous radioisotopes may be generated. Many standard alloy components, including Fe and Cr, form undesirable radiation reaction products. Thus, metals and alloys subject to neutron bombardment must be extremely pure and free of problematic elements, e.g., Na.
It is one object of the present invention to provide a radioactive coating that can be produced from less than extremely pure materials, and without placing the coated article into a nuclear reactor.
It is a further object of the present invention to provide a radioactive coating comprising any of a wide variety of radioisotopes, including insoluble radioisotopes.
It is another object of the present invention to provide a radioactive coating solution which permits separation of the radioisotope therefrom.
It is yet another object of the present invention to provide a method of making a substrate radioactive by applying one or more radioactive coating layers thereto.
It is another object of the present invention to provide radioactive coated substrates.
It is a further object of the present invention to provide substrates coated with multiple layers of radioactive coatings.
It is yet a further object of the present invention to provide a medical device, or a component of a medical device, coated with one or more radioactive coating layers.
It is a still further object of the present invention to provide a catheter having an component coated with one or more radioactive coatings layers, and more particularly, an expandable component coated with one or more radioactive coating layers.
It is still a further object of the present invention to provide a method of making a substrate having a variable radioactive coating or coatings capable of producing an asymetric radiation field.
It is yet a further object of the present invention to provide a substrate having a variable radioactive coating or coatings capable of producing an asymetric radioactive field.
It is an object of the present invention to provide a brachytherapy device coated with a variable radioactive coating or coatings capable of producing an asymetric radioactive field.
It is a further object of the present invention to provide a method of producing a radiation field corresponding to a target field.
It is a still further object of the present invention to provide a method of producing a radiation field corresponding to the morphology of a tumor.
The invention disclosed herein relates to radioactive coating solutions, radioactive sols and sol-gels, methods used to form a radioactive coatings on a substrate, and to radioactive coated substrates.
The present invention relates to a coating solution comprising, in solution, at least one carrier metal ion and a radioisotope. In a particular embodiment of the present invention, the coating solution further comprises a reducing agent. The radioisotope present in the coating solution may be soluble or insoluble or present as the insoluble compound of a radioisotope.
The present invention also relates to a method of making a substrate radioactive by applying a radioactive coating solution to the substrate to form a substrate having a radioactive coating formed thereon. In a particular embodiment of the method, the radioactive coating is a radioactive composite coating comprising a metal matrix and a radioactive dispersed phase. Methods of applying the radioactive coating solution to the substrate include electrodeposition and electroless deposition.
The present invention also relates a radioactive sols and radioactive sol-gels. The radioactive sol of the present invention comprises a metal alkoxide or other organometallic compound and a radioisotope. In a particular embodiment, the radioisotope is insoluble or the insoluble compound of a radioisotope, and is either added to the metal alkoxide or other organometallic compound prior to polymerization, or added by impregnation after partial polymerization. The present invention also relates to methods of making a substrate radioactive by applying a radioactive sol or sol-gel to a substrate to form a radioactive coating. In a particular embodiment of the present invention, the radioactive coating is a composite coating comprising an oxide matrix and a radioactive dispersed phase. Methods of applying the radioactive sol or sol-gel to the substrate include, without limitation, spin coating and dip coating.
The present invention further relates to methods of forming multiple radioactive coating layers on a substrate. Optionally, the method includes deposition of an activation layer over the substrate prior to deposition of the radioactive coating layer, such that the activation is interposed between the substrate and the radiation coating layer. In a particular embodiment, the method includes deposition of an activation layer between two radioactive coatings layers. Optionally, the method also includes deposition of a protective coating layer over the radioactive coating.
The present invention also relates to radioactively coated substrates. Suitable substrates include, but are not limited to, metals, alloys, polymers, plastics, ceramics and composites. In a particular embodiment of the present invention, the substrate is a medical device formed from such materials, or a component thereof. Representative medical devices include catheters, guidewires, stents, and brachytherapy devices. More particularly, the substrate is be a catheter component, and more particularly, the expandable component of a catheter.
The present invention also relates to a method of making a substrate having a variable radioactive coating capable of producing an asymetric radiation field, as well as to substrates having a variable radioactive coating. In a particular embodiment, the present invention relates to a brachytherapy device having a variable radioactive coating capable of producing an asymetric radiation field.
The present invention also relates to a method of producing a radiation field corresponding to a target field. In particular, the method of the present invention involves the design or selection of a brachytherapy device having a variable radioactive coating capable of producing an asymetric radiation field, which can be used alone or in combination with other such devices to produce a radiation field that closely corresponds to the morphology of a tumor.
The present invention advantageously permits production of radioactive substrates by virtue of a radioactive coating or coatings applied thereto. The present invention overcomes limitations of the traditional alloying and nuclear bombardment methods used to render metal articles radioactive to provide a radioactive metal coating which can be formed from a wide array of radioisotopes, including insoluble radioisotopes, relatively safely and inexpensively.
In particular embodiments, the present invention advantageously permits separation of a radioisotope from a radioactive coating bath, reducing the volume of the coating solution which must be treated or disposed of as radioactive waste. This feature of the present invention also permits recharging of the radioisotope, providing a further economic benefit.
In certain other embodiments, the present invention advantageously permits production of a radioactive coated brachytherapy device which can be used alone or in combination with other such devices to produce a radiation field closely corresponding to the morphology of a tumor, reducing radiation damage to adjacent normal tissue. Thus, the dose of radiation that can be given to a tumor is increased with less damage to the adjacent normal tissue than is seen with radiation doses currently in use. This will most likely result in a higher response rate of tumors to brachytherapy, and in many cases, higher patient survival rates.
These and other advantages of the present invention will be apparent to those skilled in the art in view of the disclosure set forth below.